IL-1β regulates FHL2 and other cytoskeleton- related genes in human chondrocytes
IL-1β regulates FHL2 and other cytoskeleton- related genes in human chondrocytes
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DOI：
10.2119/2007-00118.joos
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发表时间：
2008-03-01
影响因子：
5.7
通讯作者：
Brenner, Rolf E.
中科院分区：
文献类型：
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作者：
Joos, Helga;Albrecht, Wolfgang;Brenner, Rolf E.
在骨关节炎（OA）中，软骨破坏不仅与合成代谢和分解代谢过程的不平衡有关，而且与软骨细胞中细胞骨架组织的改变有关，尽管它们的发病原因迄今为止在很大程度上是未知的。因此，我们研究了促炎细胞因子IL-1 β在基因表达水平上对OA软骨细胞中细胞骨架组分的可能影响。使用全基因组阵列，我们发现IL-1 β参与许多细胞因子相关基因的调节。除了众所周知的细胞骨架成分外，还显示了编码LIM蛋白的四个基因的表达和调节。这四个基因以前在软骨细胞中未被描述。定量PCR分析证实了IL-1 β对Fhl 7、Fhl 2、Lasp 1和Pdlim I以及Tubb和Vim的显著下调。SB 203580对p38丝裂原活化蛋白激酶（MAPK）的抑制抵消了IL-1 β对Fhl 2和Tubb表达的影响，表明该信号通路部分参与。另外在蛋白质水平上证实了仅LIM蛋白FHL 2的下调。与这些结果一致，IL-1 β诱导软骨细胞的形态，细胞骨架的组织和FHL 2的细胞分布的变化。我们的结论是，L-1 β参与调节人类软骨细胞中的各种细胞骨架成分，包括多功能蛋白FHL 2。这可能与OA的发病机制有关。
In osteoarthritis (OA), cartilage destruction is associated not only with an imbalance of anabolic and catabolic processes but also with alterations of the cytoskeletal organization in chondrocytes, although their pathogenetic origin is largely unknown so far. Therefore, we have studied possible effects of the proinflammatory cytokine IL-1 beta on components of the cytoskeleton in OA chondrocytes on gene expression level. Using a whole genome array, we found that IL-1 beta is involved in the regulation of many cytoskeleton-related genes. Apart from well-known cytoskeletal components, the expression and regulation of four genes coding for LIM proteins were shown. These four genes were previously undescribed in the chondrocyte context. Quantitative PCR analysis confirmed significant downregulation of Fhl7, Fhl2, Lasp 1, and Pdlim I as well as Tubb and Vim by IL-1 beta. Inhibition of p38 mitogen-activated protein kinase (MAPK) by SB203580 counteracted the influence of IL-1 beta on Fhl2 and Tubb expression, indicating partial involvement of this signaling pathway. Downregulation of the LIM-only protein FHL2 was confirmed additionally on the protein level. In agreement with these results, IL-1 P induced changes in the morphology of chondrocytes, the organization of the cytoskeleton, and the cellular distribution of FHL2. We conclude that L-1 beta is involved in the regulation of various cytoskeletal components in human chondrocytes including the multifunctional protein FHL2. This might be relevant for the pathogenesis of OA.